Is COL2A1 p.Arg515= (c.1545C>T) pathogenic?

COL2A1 p.Arg515= (c.1545C>T) is classified Likely benign in COL2A1 (ClinVar, Multiple submitters, 2 submitters; last evaluated 2025-11-24). Ultra-rare (popmax 0.0178%, sas).

How common is COL2A1 p.Arg515= (c.1545C>T) in the general population?

COL2A1 p.Arg515= (c.1545C>T) is ultra-rare (popmax 0.0178%, sas) (gnomAD).

COL2A1 p.Arg515=

c.1545C>T · rs41317925 · VCV1157930

Likely benign Multiple submitters

Classification

Likely benign

ClinVar

Review

Multiple submitters ★★☆☆

ClinVar · 2 submitters

gnomAD v4.1

Rare

ultra-rare (popmax 0.0178%, sas)

Computational evidence

Protein change
Missense predictors do not apply to this variant type; conservation carries the signal.
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP -0.3	GERP -3.8, phastCons 0.001
Overall
CADD	1.888	PHRED · no single calibrated threshold — expert panels disagree

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.0178% South Asian · 15/84,076 alleles

Filtering AF 0.011% ClinGen BA1/BS1 input FAF95, joint · FAF99 0.00886%

Overall 0.00193% 30/1,551,642 alleles · ultra-rare

Ancestry group	Frequency	1 in
South Asiangrpmax	0.0178%	5,605
African / African-American	0.0041%	24,377
Admixed American	0.00196%	51,016
Remaining individualsnot grpmax-eligible	0.00166%	60,112
European (non-Finnish)	0.000872%	114,701

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: COL2A1
Protein: p.Arg515=
Coding: c.1545C>T
MANE Select: NM_001844
dbSNP: rs41317925
Type: single nucleotide variant
Location: chr12:47985948 (GRCh38)
Gene constraint: LOEUF 0.183 · pLI 1.00 · ClinGen HI 3/3 (gnomAD)
Structure: AlphaFold pLDDT 53.56 · 11 PDB
Residue 515: the 'disordered' region; the 'triple-helical region' region

Full COL2A1 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Similar variants

COL2A1 p.Arg515Cys Uncertain significance ★★ ⚠ same residue
COL2A1 p.Arg515His Uncertain significance ★★ ⚠ same residue
COL2A1 c.1023+1G>A Pathogenic ★★ same type
COL2A1 c.1024-2A>C Pathogenic ★★ same type
COL2A1 c.1069-2A>G Pathogenic/Likely pathogenic ★★ same type
COL2A1 c.1221+1G>A Pathogenic ★★ same type
COL2A1 c.1222-2A>G Pathogenic ★★ same type
COL2A1 c.1365+1G>A Pathogenic/Likely pathogenic ★★ same type

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/col2a1-p-arg515 (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown